Synthesis of dehydrophytol and vitamin E

Abstract

A process for the synthesis of dehydrophytol and Vitamin E comprising forming a C 15 acetylene from hexahydropseudoionone and then coupling said acetylene with 1-acetoxy-4-chloro-3-methylbut-2-ene to form a C 20 acetoxy-enyne. The latter is readily subjected to partial hydrogenation and saponification in that order to form a dehydrophytol, a useful intermediate for the synthesis of Vitamin E and other products.

Having thus described the invention, what is claimed is: 
     
       1. A process for the synthesis of dehydro-Vitamin E comprising the steps of a. reacting hexahydropseudo-ionone with a metal acetylide to form 3,7,11-trimethyl-3-hydroxy-1-dodecyne;   b. reacting the product of step a) with a reagent capable of replacing the hydroxyl group with a halogen to produce 3,7,11-trimethyl-3-halo-1-dodecyne;   c. reducing the product of step b) to form the corresponding allene, said allene being 3,7,11-trimethyldodeca-1,2-diene;   d. isomerizing the allene of step c) to 3,7,11-trimethyldodeca-1-yne in the presence of a strong base;   e. coupling the acetylene of paragraph d) with a reactant having the general formula ##STR8## wherein R 3  is a halogen and R 1  is an hydroxyl or carboxylic acid ester group;   f. hydrogenating and saponifying the coupling product to dehydrophytol; and   g. coupling the product of step (f) with trimethylhydroquinone.   
     
     
       2. The process of claim 1 wherein step c) is carried out by dissolving the product of step b) in a mixture of glacial acetic acid and zinc in at least stoichiometric proportions based on the amount of the dodecyne of step b). 
     
     
       3. The process of claim 1 wherein the base of step d) is a solution of sodium amide in ethylene diamine-ether. 
     
     
       4. The process of claim 1 wherein said reagent of step (b) is hydrochloric acid. 
     
     
       5. The process of claim 1 wheein the coupling reaction of step e) is carried out by reacting the acetylene product of step d) successively with a Grignard reagent in the presence of an aprotic solvent and then a cuprous salt, in that order, to form the cuprous salt of the acetylene, and then reacting the cuprous salt product with the coupling reactant of step e), also in the presence of an aprotic solvent. 
     
     
       6. The process of claim 1 for the synthesis of Vitamin E wherein the dehydro-Vitamin E is hydrogenated to Vitamin E. 
     
     
       7. The process of claim 1 wherein the reactant of step (e) is 1-acetoxy-4-chloro-3-methylbut-2-ene.